The 24-hour-a-day, 7-day a week, work-world arrived within our lifetimes, and is here to stay. Americans are working more and more, frequently at multiple jobs. The pattern of short sleep during the week followed by attempts to recover on the weekend is in common practice, but we know little of the associated health risks. What is the cost in terms of increasing known risk markers for cardiovascular disease, of repeated nights of insufficient sleep, and is this cost compounded with repetition, without adequate recovery? Evidence is accumulating to suggest that short sleep duration is linked to the development of metabolic and inflammation-associated diseases, such as cardiovascular disease. Mechanisms involved in the development of cardiovascular disease include impaired vascular function and inflammation. The current application is designed to investigate the effects of repeated periods of short nocturnal sleep duration in 4 cycles (each cycle consisting of 3 nights of 4 hours of sleep opportunity per night), and each cycle of short sleep followed by a single night of recovery sleep. Vascular reactivity will be assessed using brachial artery flow mediated dilation, and microcirculatory vasodilation will be assessed using perfusion imaging techniques. The dependence of IL-6 and sVCAM-1 as measured in peripheral circulation, on vascular function, will also be investigated. PUBLIC HEALTH RELEVANCE: The current study is designed to investigate the effects of repeated periods of short nocturnal sleep duration in 4 cycles (each cycle consisting of 3 nights of 4 hours of sleep per night), and each cycle of short sleep followed by a single night of recovery sleep. We will investigate the effects of repetitive cycles of sleep loss on vascular functioning, and on IL-6 and sVCAM-1. We will test for evidence of a progressive increase in the basal levels of IL-6 and sVCAM-1, and will also test for increasing sensitization to sleep loss responses over multiple cycles of sleep loss. This study will test the mechanisms linking sleep loss and key risk markers for cardiovascular disease.